Q&A #14: Are the C-19 unvaccinated ‘more’ or ‘less’ susceptible to contracting severe disease from avian influenza and monkeypox?

In my opinion, there can be no doubt that 'C-19 pandemic-experienced' C-19-unvaccinated people are much less susceptible to severe disease from avian influenza and monkeypox. This is because they got an opportunity to train their cell-mediated innate immunity (i.e., NK cells) during the pandemic. Training basically results in the enhanced recognition of virus-derived self-mimicking peptides (VSMPs) that are expressed at the surface of virus-infected host cells at an early stage of infection (i.e., before viral progeny is produced). There is a high level of similarity between the VSMPs derived from Coronaviruses and those derived from orthopox viruses (both, influenza viruses and monkeypox, smallpox, cowpox belong to the genus Orthopoxvirus). It is, therefore, reasonable to assume that NK cells from Coronavirus-experienced, unvaccinated people will be well prepared to also tackle orthopox viruses. This will leave enough time for the adaptive immune system to finally eliminate avian influenza virus and monkeypox virus via poorly MHC class I-restricted CD8+ T cells. However, if the infectious pressure is high, these viruses might still cause disease (but not severe) in the unvaccinated. On the other hand, as monkeypox and avian flu only spread via people with symptoms, isolation and quarantining of people with symptoms should dramatically reduce viral pressure. So, the unvaccinated should be fine.

Even fully vaccinated people will still present VSMPs at the surface of their SC-2-infected epithelial cells. However, high levels of (continuously boosted) infection-enhancing Abs will raise viral infectiousness to levels that simply overload the cell-based innate immune system. The innate immune system serves the purpose of '1st line' of immune defense and cannot cope with a high viral load without calling in the 'special forces' of the adaptive immune system. In vaccinees, however, the latter (Ag-specific IgGs and MHC-unrestricted CD8+ T cells) are already stretched beyond the affordable limits in a desperate attempt to eliminate the virus. There is, therefore, no further room for them to come to the aid of the NK cells to clear other viruses from the body. If you want to read more about the critical role of NK cells in the immune response to Sars-CoV-2, please consult my website: https://www.voiceforscienceandsolidarity.org/

‍In conclusion, as an unvaccinated healthy individual with adequately trained NK cells, I wouldn't worry too much about getting severely ill from monkeypox or avian flu. So, the unvaccinated who did not get the smallpox shot in the past, should not panic as they may just get away with mild or, at worst, moderate illness (depending on level of epigenetic NK cell training and their overall health status). And BTW, be careful with the smallpox vaccines as only replication-competent vaccine can be used; replication-incompetent orthopox vaccines induce Abs that because of the different surface decoration of monkeypox as compared to cowpox/ vaccinia (i.e., the poxvirus used in the smallpox vaccine) may enhance people's susceptibility to ADEI upon subsequent exposure to monkeypox. On the other hand, live attenuated, replication-incompetent monkeypox vaccine will not enable NK cell training!